title: Discovery of triazines as potent, selective and orally active PDE4 inhibitors.
abstract: Expanding on HTS hit 4 afforded a series of [1,3,5]triazine derivatives as novel PDE4 inhibitors. The SAR development and optimization process with the emphasis on ligand efficiency and physicochemical properties led to the discovery of compound 44 as a potent, selective and orally active PDE4 inhibitor.
authors.affiliation: BioCrea GmbH, Meissner Strasse 191, 01445 Radebeul, Germany. rainer.gewald@telecolumbus.net
authors.forename: Rainer
authors.initials: R
authors.lastname: Gewald
authors.forename: Christian
authors.initials: C
authors.lastname: Grunwald
authors.forename: Ute
authors.initials: U
authors.lastname: Egerland
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001665:Binding Sites; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4 / Q000737:chemistry / Q000378:metabolism*; D054708:Cyclic Nucleotide Phosphodiesterases, Type 7 / Q000037:antagonists & inhibitors / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D006207:Half-Life; D008862:Microsomes, Liver / Q000378:metabolism; D062105:Molecular Docking Simulation; D058988:Phosphodiesterase 4 Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D017434:Protein Structure, Tertiary; D051381:Rats; D013329:Structure-Activity Relationship; D014227:Triazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics
chemical_list: D058988:Phosphodiesterase 4 Inhibitors; D014227:Triazines; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D054708:Cyclic Nucleotide Phosphodiesterases, Type 7; C517458:PDE7A protein, human